(a) Field of the Invention
This invention relates to 2H-imidazo[4,5-b]pyridin-2-ones or -2-thiones, their preparation and their use as cardiotonics.
(b) Description of the Prior Art
Baldwin et al. [J. Med. Chem. 20, 1189-1193 (1977)] prepared 2-(3-pyridinyl)-1H-imidazo[4,5-b]pyridine and 2-(4-pyridinyl)-1H-imidazo[4,5-b]pyridine by heating, respectively, a mixture of 2,3-diaminopyridine and nicotinic acid or a mixture of 2,3-diminopyridine and isonicotinic acid. Both of these compounds were found by Baldwin et al. to be inactive when tested as inhibitors of xanthine oxidase.
Lesher and Gruett British Pat. No. 1,322,318, published July 4, 1973, shows as intermediates for preparing antibacterially-active 1-alkyl-1,4-dihydro-4-oxo-7-PY-1,8-naphthyridine-3-carboxylic acids and esters (where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents) the following illustrative reaction sequence (Examples 1C through 1G and 2C through 2G): the preparation of 1,2-dihydro-2-oxo-6-(4- or 3-pyridinyl)nicotinonitrile, its hydrolysis and decarboxylation to produce 6-(4- or 3-pyridinyl)-2(1H)-pyridinone, its chlorination with phosphorus oxychloride to produce 2-chloro-6-(4- or 3-pyridinyl)pyridine, its reaction with hydrazine to produce 2-hydrazino-6-(4- or 3-pyridinyl)pyridine and its catalytic hydrogenation using Raney nickel to produce 2-amino-6-(4- or 3-pyridinyl)pyridine also useful as an intermediate to produce said antibacterially-active 1,8-naphthyridines.
Brundage and Lesher U.S. Pat. No. 3,838,156, issued Sept. 24, 1974, discloses as sequential intermediates 1,2-dihydro-2-oxo-6-Q'"-nicotinic acids, 2-halo-6-Q'"-nicotinic acids and 2-RNH-6-Q'"-nicotinic acids, where Q'" is 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents, halo is chloro or bromo, and R is lower-alkyl.
Lesher and Opalka U.S. Pat. No. 4,072,746, issued Feb. 7, 1978, discloses the following reaction sequences:
(a) hydrolysis of 1,2-dihydro-2-oxo-5-PY-nicotinonitrile to produce 1,2-dihydro-2-oxo-5-PY-nicotinic acid, decarboxylation of said nicotinic acid to produce 5-PY-2(1H)-pyridinone, nitration of either said nicotinic acid or said 2(1H)-pyridinone to produce 3-nitro-5-PY-2(1H)-pyridinone and reduction of the 3-nitro compound to produce 3-amino-5-PY-2(1H)-pyridinone; and,
(b) the reaction of 5-PY-2(1H)-pyridinone with halogen, preferably bromine or chlorine, to produce 3-halo-5-PY-2(1H)-pyridinone and reacting said halo compound with R.sub.1 R.sub.2 NH to produce 3-R.sub.1 R.sub.2 N-5-PY-2(1H)-pyridinone. In the above two reaction sequences R.sub.1 is lower-alkyl, R.sub.2 is hydrogen or lower-alkyl and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. Of the various compounds in said two sequences, the 3-amino-5-PY-2(1H)-pyridinones, 3-R.sub.1 R.sub.2 N-5-PY-2(1H)-pyridinones, the 1,2-dihydro-2-oxo-5-PY-2(1H)-nicotinonitriles and the 5-PY-2(1H)-pyridinones had cardiotonic activity; all others were intermediates as were the 1,2-dihydro-2-oxo-5-PY-2(1H)-nicotinonitriles and 5-PY-2(1H)-pyridinones.